改写In the mechanism FSP1 catalyzes the regeneration of COQ10 by through the use of NADPH and the FSP1-COQ10-NADPH pathway is an independent parallel system that cooperates with glutathione and GPX4 to

The FSP1-COQ10-NAD(P)H pathway is a parallel system that operates independently to cooperate with glutathione and GPX4 in suppressing ferroptosis. FSP1 catalyzes the regeneration of COQ10 through the use of NADPH, acting on the plasma membrane. Meanwhile, DHODH is identified as a mitochondrial inhibitor of ferroptosis, reducing CoQ10 to ubiquinol within mitochondria, similar to the function of FSP1 in extramitochondrial membranes. These findings suggest that the production of CoQ10 in different organelles has the ability to inhibit ferroptosis, but whether this defense mechanism is tumor type-specific remains an unresolved question. Furthermore, GCH1, the rate-limiting enzyme in the biosynthesis of BH4, has been identified as a suppressor of ferroptosis. BH4 functions similarly to CoQ10, exerting potent antioxidant effects to prevent lipid peroxidation, and is also used in the synthesis of CoQ10. GCH1 overexpression leads to an increase in the abundance of reduced CoQ10, remodeling the lipid membrane environment and suppressing sensitivity to ferroptosis.